Bypassing the bottleneck: Intentional hepatitis C transmission with organ transplant

Abstract

Solid organ transplantation from hepatitis C virus–positive (HCV-positive) deceased donors into HCV-negative recipients is a recent approach aimed to expand the donor organ pool in the setting of severe shortage. Good short-term outcomes have been reported with this approach in combination with direct-acting antivirals. In this issue of the JCI, Zahid and colleagues have characterized early viral kinetics and the genetic landscape of donor-to-recipient HCV transmission using single-genome sequencing. In seven HCV-negative recipients of four HCV-positive donor organs, productive infection with a highly diverse viral population was seen by day three after transplant. The degree of genetic diversity seen in recipients of HCV-positive organs was unlike the narrow genetic bottleneck typically observed with acute HCV acquisition from intravenous drug use or sexual activity. All recipients achieved HCV cure with treatment. The consequences of acute infection with a genetically diverse HCV population are unknown; however, early clinical experience with this transplantation strategy is promising.